On January 17, 2013 she and husband Kevin O’Leary welcomed twins, a son, Ellis James, and a daughter, Elizabeth Mae, in Brooklyn, N.Y. Ellis weighed in at 6 lbs., 10 oz. and was 19.25 inches long, while Elizabeth weighed in at 5 lbs., 12 oz. and was 19 inches long.[4]

Brown's early career included working in commercials, notably playing the spokesperson "Wendy Wire" for a company called Century Cable. She appeared in the HP Pavilion "Computer is Personal Again" commercials.[5] Additionally, she is the spokesperson for ECCO shoes.[6] and was also a spokesperson in a 2009 commercial for Cedar Point amusement park. She is involved in the comedy sketch group "Mouth", based in New York, where she has lived for over 12 years.

In 1999 and 2000, the Travel Channel was looking for a travel host, and Brown was chosen after a series of auditions. In her role of host, she introduces viewers to vacation destinations and hotels in the United States and around the world, as well as showcasing restaurants and activities at those destinations.[7] As a travel host, Brown travels 230 days out of the year and takes eight days to film an hour-long episode.[8]

In addition to her regular shows, Brown hosted several Travel Channel specials, such as the 2006 all-access special Great Cruises: Freedom of the Seas with Samantha Brown aboard the Freedom of the Seas cruise ship, the largest passenger ship in the world at the time of its launch. Prior to that, she hosted a 12-night Mediterranean Venice cruise aboard the Brilliance of the Seas cruise ship. The accompanying show was titled Samantha Brown's First Cruise. In 2007, she hosted a special titled Passport to Green Getaways, a travelogue to three eco-friendly destinations in North America.

In 2007, Brown had two shows in production. In April 2007, Discovery Networks announced that she would host a new series titled Passport to Great Weekends ... With Samantha Brown featuring Brown exploring 48-hour vacation locations in the US and abroad. In September 2007, she was in Beijing, filming Passport to China, which aired in July 2008, just ahead of the Beijing Olympics.[9]

In 2008, Brown debuted Passport to Great Weekends, which showcased her in a more informal light as well as following her on more unique, off-the-beaten-path vacations. Episodes would follow the format of her arrival at a destination on a Friday afternoon and conclude with her leaving on Sunday evening. The second season's title was changed to Samantha Brown's Great Weekends and featured a new introduction, but mostly the same format.

On February 8, 2010, the Travel Channel presented "Samantha Brown's 10th Anniversary Special" to commemorate Brown's ten years as host.

On April 9, 2010, she made a special guest appearance on The Price Is Right to present a travel-themed showcase.

On July 12, 2010, her most recent series on the Travel Channel was released, "Samantha Brown's Asia."

In Anthony Bourdain's "Christmas Special" episode of No Reservations, first aired in the U.S. on December 12, 2011, Samantha Brown appeared in a segment that satirized both her persona and the supposed conflict between the "perky" Brown and the "edgy" Bourdain. In the same month, more in keeping with her wholesome "girl next door" image, Brown hosted a video tour of the new Disney resort in Hawaii, which was produced and released by Disney to promote the Disney Vacation Club.

In the summer of 2013, Samantha shot a new pilot for the Travel Channel in the Yellowstone area but Brown tweeted at the time that she could not talk about it for fear of jinxing the project. The project later proved to be two sample episodes of "Samantha Brown's Cash Attack," a travel-related game show.[10] Brown ambushed tourists in popular travel destinations and gave them an opportunity to win cash by answering questions related to the area and/or performing travel challenges. The two episodes aired on November 26, 2013. A decision regarding the production of more episodes is pending.

Brown will serve as a co-host of The Trip: 2014, a sweepstakes event that will take viewers on a trip through Spain and Morocco.[11]

Brown was also a co-host for The Trip: 2015 in Hawaii, which originally aired in February 2015.

Brown will next be seen in the Travel Channel series 50/50 with co-host Chris Grundy in 2015.[12]